Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling
It is well established that altered purinergic signaling contributes to vascular dysfunction in type 2 diabetes (T2D). Red blood cells (RBCs) serve as an important pool for circulating ATP and the release of ATP from RBCs in response to physiological stimuli is impaired in T2D. We recently demonstra...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.603226/full |
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| author | Ali Mahdi Yahor Tratsiakovich John Tengbom Tong Jiao Lara Garib Michael Alvarsson Jiangning Yang John Pernow John Pernow Zhichao Zhou |
| author_facet | Ali Mahdi Yahor Tratsiakovich John Tengbom Tong Jiao Lara Garib Michael Alvarsson Jiangning Yang John Pernow John Pernow Zhichao Zhou |
| author_sort | Ali Mahdi |
| collection | DOAJ |
| description | It is well established that altered purinergic signaling contributes to vascular dysfunction in type 2 diabetes (T2D). Red blood cells (RBCs) serve as an important pool for circulating ATP and the release of ATP from RBCs in response to physiological stimuli is impaired in T2D. We recently demonstrated that RBCs from patients with T2D (T2D RBC) serve as key mediators of endothelial dysfunction. However, it remains unknown whether altered vascular purinergic signaling is involved in the endothelial dysfunction induced by dysfunctional RBCs in T2D. Here, we evaluated acetylcholine-induced endothelium-dependent relaxation (EDR) of isolated rat aortas after 18 h ex vivo co-incubation with human RBCs, and aortas of healthy recipient rats 4 h after in vivo transfusion with RBCs from T2D Goto-Kakizaki (GK) rats. Purinergic receptor (PR) antagonists were applied in isolated aortas to study the involvement of PRs. EDR was impaired in aortas incubated with T2D RBC but not with RBCs from healthy subjects ex vivo, and in aortas of healthy rats after transfusion with GK RBCs in vivo. The impairment in EDR by T2D RBC was attenuated by non-selective P1R and P2R antagonism, and specific A1R, P2X7R but not P2Y6R antagonism. Transfusion with GK RBCs in vivo impaired EDR in aortas of recipient rats, an effect that was attenuated by A1R, P2X7R but not P2Y6R antagonism. In conclusion, RBCs induce endothelial dysfunction in T2D via vascular A1R and P2X7R but not P2Y6R. Targeting vascular purinergic singling may serve as a potential therapy to prevent endothelial dysfunction induced by RBCs in T2D. |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T01:04:54Z |
| publishDate | 2020-11-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-47c238800521420bbd4c379ce5be2aab2022-12-21T22:09:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.603226603226Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic SignalingAli Mahdi0Yahor Tratsiakovich1John Tengbom2Tong Jiao3Lara Garib4Michael Alvarsson5Jiangning Yang6John Pernow7John Pernow8Zhichao Zhou9Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Endocrinology and Diabetology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Cardiology, Karolinska University Hospital, Stockholm, SwedenDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, SwedenIt is well established that altered purinergic signaling contributes to vascular dysfunction in type 2 diabetes (T2D). Red blood cells (RBCs) serve as an important pool for circulating ATP and the release of ATP from RBCs in response to physiological stimuli is impaired in T2D. We recently demonstrated that RBCs from patients with T2D (T2D RBC) serve as key mediators of endothelial dysfunction. However, it remains unknown whether altered vascular purinergic signaling is involved in the endothelial dysfunction induced by dysfunctional RBCs in T2D. Here, we evaluated acetylcholine-induced endothelium-dependent relaxation (EDR) of isolated rat aortas after 18 h ex vivo co-incubation with human RBCs, and aortas of healthy recipient rats 4 h after in vivo transfusion with RBCs from T2D Goto-Kakizaki (GK) rats. Purinergic receptor (PR) antagonists were applied in isolated aortas to study the involvement of PRs. EDR was impaired in aortas incubated with T2D RBC but not with RBCs from healthy subjects ex vivo, and in aortas of healthy rats after transfusion with GK RBCs in vivo. The impairment in EDR by T2D RBC was attenuated by non-selective P1R and P2R antagonism, and specific A1R, P2X7R but not P2Y6R antagonism. Transfusion with GK RBCs in vivo impaired EDR in aortas of recipient rats, an effect that was attenuated by A1R, P2X7R but not P2Y6R antagonism. In conclusion, RBCs induce endothelial dysfunction in T2D via vascular A1R and P2X7R but not P2Y6R. Targeting vascular purinergic singling may serve as a potential therapy to prevent endothelial dysfunction induced by RBCs in T2D.https://www.frontiersin.org/articles/10.3389/fphar.2020.603226/fullerythrocyteendothelial dysfunctiondiabetespurinergic receptoradenosine triphosphateadenosine |
| spellingShingle | Ali Mahdi Yahor Tratsiakovich John Tengbom Tong Jiao Lara Garib Michael Alvarsson Jiangning Yang John Pernow John Pernow Zhichao Zhou Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling Frontiers in Pharmacology erythrocyte endothelial dysfunction diabetes purinergic receptor adenosine triphosphate adenosine |
| title | Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling |
| title_full | Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling |
| title_fullStr | Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling |
| title_full_unstemmed | Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling |
| title_short | Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling |
| title_sort | erythrocytes induce endothelial injury in type 2 diabetes through alteration of vascular purinergic signaling |
| topic | erythrocyte endothelial dysfunction diabetes purinergic receptor adenosine triphosphate adenosine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.603226/full |
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